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BACKGROUND: Common variable immunodeficiency is the most prevalent symptomatic primary immunodeficiency in adults. Affected patients fail to mount an appropriate humoral response against community acquired infectious diseases and recent reports have provided data supporting the increased susceptibility of these patients to severe SARS-CoV-2 infections. In this context, the infusion of COVID-19 convalescent plasma could represent an effective therapeutic strategy. CASE PRESENTATION: 25-year old woman diagnosed with common variable immunodeficiency in 2013, developed severe COVID-19 that rapidly progressed to pneumonia presenting with multiple bilateral lung opacities that were both central and peripheral and presented as ground-glass and consolidation types involving all lobes, bilaterally. As blood oxygen saturation decayed and lung abnormalities were not responsive to large spectrum antibiotics and corticosteroids, patient was placed on mechanical ventilation and compassionate-use of approved COVID-19 convalescent donor plasma was introduced. The patient presented a rapid response to the approach and mechanical ventilation could be interrupted 24 h after first dose of COVID-19 convalescent donor plasma. As a whole, the patient received four doses of 200 mL convalescent plasma during a period of 6 days. There was rapid improvement of clinical status, with interruption of supplemental oxygen therapy after 6 days and reduction of lung abnormalities as evidence by sequential computed tomography scans. CONCLUSIONS: This is a single patient report that adds to other few reports on common variable immunodeficiency and agammaglobulinemia, suggesting that COVID-19 convalescent donor plasma could be a valuable therapeutic approach to treat patients affected by dysgammaglobulinemias and presenting severe COVID-19.

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AIMS: Correlate clinical and histologic features with renal outcome in patients with biopsy-proven IgA nephropathy (IgAN). MATERIALS AND METHODS: Retrospective analysis of records and renal tissue of IgAN patients. Histology was revised according to MEST score of Oxford classification. Focal segmental glomerulosclerosis (FSGS) features were assessed by light microscopy. Electron microscopy review searched for podocyte effacement. RESULTS: 67 patients were included, 56.7% men, mean age 34.5 ± 12.5 years, mean arterial pressure (MAP) 106 ± 18 mmHg, estimated glomerular filtration rate (eGFR) 63.32 ± 43.07 mL/min/1.73m2 and proteinuria 3.1 ± 2.2 g/24 h. M1 was seen in 38 patients (56.7%), E1 in 12 (17.9%), S1 in 49 (73.1%), T1 in 18 (26.8%), and T2 in 17 (25.3%). Mean effacement index (EI) was 0.81 ± 0.18 and did not correlate with proteinuria. 27 patients (40.2%) had end-stage renal disease (ESRD) which correlated with MAP (p = 0.002), eGFR (p = 0.0003), T1 (p = 0.0008) and T2 (p = 0.0001), follow-up MAP (p = 0.02) and follow-up proteinuria (p = 0.01 for 1.0 - 4.0 g/24 h and p = 0.005 for ≥ 4.0 g/24 h). T score correlated with MAP and proteinuria at baseline (p = 0.0001 and 0.0097, respectively) and during follow-up (p = 0.0001 and < 0.0001, respectively). Podocyte hypertrophy correlated with MAP at baseline and during follow-up (p = 0.0046 and 0.0295, respectively). Tip lesion correlated with MAP at baseline (p = 0.0228). There was no correlation between FSGS features or EI with proteinuria or ESRD. CONCLUSIONS: Our data corroborate eGFR, proteinuria, MAP and T score as risk factors for ESRD in IgAN. Most patients had diffuse podocyte effacement, probably secondary to factors unrelated to proteinuria.
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Obesity and type 2 diabetes are characterized by insulin resistance, and the common basis of these events is a chronic and systemic inflammatory process marked by the activation of the c-Jun N-terminal kinase (JNK) and inhibitor-κB kinase (IKKß)/nuclear factor-κB (NFκB) pathways, up-regulated cytokine synthesis, and endoplasmic reticulum dysfunction. The aim of this study was to evaluate the effects of diacerhein administration, an antiinflammatory drug that reduces the levels of inflammatory cytokines, on insulin sensitivity and signaling in diet-induced obese (DIO) mice. Swiss mice were fed with conventional chow (control group) or a high-fat diet (DIO group). Later, DIO mice were randomly subdivided into a new subgroup (DAR) that received 20 mg/kg diacerhein for 10 d. Western blotting was used to quantify the expression and phosphorylation of insulin receptor, insulin receptor substrate 1, and Akt and of inflammatory mediators that modulate insulin signaling in a negative manner (IKKß, JNK, and inducible nitric oxide synthase). We show here, for the first time, that the administration of diacerhein in DIO mice improved endoplasmic reticulum stress, reduced JNK and IKKß phosphorylation, and resulted in a marked improvement in fasting glucose, a decrease in macrophage infiltration in adipose tissue, and a reduced expression and activity of proinflammatory mediators accompanied by an improvement in the insulin signaling mainly in the liver and adipose tissue. Taken together, these results indicate that diacerhein treatment improves insulin sensitivity in obesity, mediated by the reversal of subclinical inflammation, and that this drug may be an alternative therapy for insulin resistance.

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Phosphatidylcholine-based magnetoliposomes containing specific ligands for biological molecules, so-called affinity magnetoliposomes (AML), may prove to be useful as adsorbents in applications such as diagnosis or anchoring and delivery of drugs at specific sites in the human body. In the present study, the performance of affinity magnetoliposomes to adsorb anticardiolipin antibodies (aCL) from a previously characterized pool of patients with autoimmune diseases is described. The magnetic vesicles were prepared by enrobing nanometer-sized colloidal magnetite particles with a phospholipid bilayer composed of dimyristoylphosphatidylcholine (DMPC) and the affinity lipid ligand cardiolipin (CL). Adsorption of antibodies onto the affinity magnetoliposomes assayed using a high-gradient magnetophoresis (HGM) system, in which the magnetoliposomes were first magnetically captured on stainless steel fibers, and which were subsequently overflowed either with a pool of sera from autoimmune patients or sera of healthy individuals as a control. The spectrophotometric assay showed stronger changes in absorbance spectra when the affinity magnetoliposomes containing cardiolipin were added to sera of autoimmune patients than when they were added to sera of healthy individuals. The breakthrough curves obtained from a frontal analyses of the adsorption in the magnetophoresis system showed a 10% difference for total adsorbed IgG when sera of autoimmune and healthy individuals were assayed on magnetoliposomes containing cardiolipin.

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This work investigated the potential use of an alternative adsorbent to anti-immunoglobulin E (IgE)-agarose for IgE selective adsorption therapy. A screening of several commercially available adsorbents (Concanavalin A, Lens culinaris[Lc], d-tryptophan, poly-l-lysine, and aminohexyl immobilized on agarose) was done through batch system assays, considering some criteria, such as adsorption capacity, selectivity, and biocompatibility. In the Lc-agarose adsorbent, total IgE, and specific IgE--for the airborne allergens Dermatophagoides pteronyssinus and Blomia tropicalis--were significantly better removed (63, 58, and 59%, respectively) than immunoglobulin G (19%), immunoglobulin A (33%), immunoglobulin M (9%), and albumin (18%). This adsorbent was packed into a column and the effect of superficial velocity, ratio of plasma volume to bed volume, number of perfusions, and temperature on IgE adsorption were evaluated. In vitro simulation of therapeutic adsorption (single perfusion) indicated that about 50% of total IgE could be eliminated.

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Kinins are potent vasoactive peptides generated in blood and tissues by the kallikrein serine proteases. Two distinct kinin receptors have been described, one constitutive (subtype B2) and one inducible (subtype B1), and many physiological functions have been attributed to these receptors, including glucose homeostasis and control of vascular permeability. In this study we show that mice lacking the kinin B1 receptor (B1-/- mice) have lower fasting plasma glucose concentrations but exhibit higher glycemia after feeding when compared to wild-type mice. B1-/- mice also present pancreas abnormalities, characterized by fewer pancreatic islets and lower insulin content, which leads to hypoinsulinemia and reduced insulin release after a glucose load. Nevertheless, an insulin tolerance test indicated higher sensitivity in B1-/- mice. In line with this phenotype, pancreatic vascular permeability was shown to be reduced in B1 receptor-ablated mice. The B1 agonist desArg9bradykinin injected intravenously can induce the release of insulin into serum, and this effect was not observed in the B1-/- mice or in isolated islets. Our data demonstrate the importance of the kinin B1 receptor in the control of pancreatic vascular homeostasis and insulin release, highlighting a new role for this receptor in the pathogenesis of diabetes and related diseases.

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Obesity has reached epidemic proportions in several regions of the world. General changes in lifestyle, including consumption of fat-rich food, are among the most important factors leading to an unprecedented increase in the prevalence of this disease. Weight gain results from an imbalance between caloric intake and energy expenditure. Both of these parameters are under the tight control of specialized neurons of the hypothalamus that respond to peripheral anorexigenic and adipostatic signals carried by leptin and insulin. Here we show, by macroarray analysis, that high-fat feeding [hyperlipidic diet (HL)] induces the expression of several proinflammatory cytokines and inflammatory responsive proteins in hypothalamus. This phenomenon is accompanied by increased activation of c-Jun N-terminal kinase and nuclear factor-kappaB. In addition, HL feeding leads to impaired functional and molecular activation of the insulin-signaling pathway, which is paralleled by increased serine phosphorylation of the insulin receptor and insulin receptor substrate-2. Intracerebroventricular treatment of HL rats with a specific inhibitor of c-Jun N-terminal kinase (SP600125) restores insulin signaling and leads to a reduced caloric intake and weight loss. We conclude that HL feeding induces a local proinflammatory status in the hypothalamus, which results in impaired anorexigenic insulin signaling.

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Allergenic extracts were produced from Drechslera (Helminthosporium) monoceras biomass cultured by solid-state fermentation using wheat bran as the substrate. The main fermentation variables were selected by statistical design, and the optimized biomass yield (1.43 mg/[g of dry substrate d]) was obtained at pH 9.5 and 45.8% moisture. The allergenic extracts were produced from crude extract by protein precipitation and polyphenol removal. Proteins in the range of 16-160 kDa were identified in the extracts. Their reactions in patients were characterized by in vivo cutaneous tests (positive in 40% of the atopic patients) and by dot-blotting assays.

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